Search

Objective: Although remarkable strides have been made in fetal medicine and the prenatal diagnosis of congenital heart disease, around 60% of newborns with isolated coarctation of the aorta (CoA) are not identified prior to birth. The prenatal detection of CoA has been shown to have a notable impact on survival rates of affected infants. To this end, implementation of artificial intelligence (AI) in fetal ultrasound may represent a groundbreaking advance. We aimed to investigate whether the use of automated cardiac biometric measurements with AI during the 18–22‐week anomaly scan would enhance the identification of fetuses that are at risk of developing CoA. Methods: We developed an AI model capable of identifying standard cardiac planes and conducting automated cardiac biometric measurements. Our data consisted of pregnancy ultrasound image and outcome data spanning from 2008 to 2018 and collected from four distinct regions in Denmark. Cases with a postnatal diagnosis of CoA were paired with healthy controls in a ratio of 1:100 and matched for gestational age within 2 days. Cardiac biometrics obtained from the four‐chamber and three‐vessel views were included in a logistic regression‐based prediction model. To assess its predictive capabilities, we assessed sensitivity and specificity on receiver‐operating‐characteristics (ROC) curves. Results: At the 18–22‐week scan, the right ventricle (RV) area and length, left ventricle (LV) diameter and the ratios of RV/LV areas and main pulmonary artery/ascending aorta diameters showed significant differences, with Z‐scores above 0.7, when comparing subjects with a postnatal diagnosis of CoA (n = 73) and healthy controls (n = 7300). Using logistic regression and backward feature selection, our prediction model had an area under the ROC curve of 0.96 and a specificity of 88.9% at a sensitivity of 90.4%. Conclusions: The integration of AI technology with automated cardiac biometric measurements obtained during the 18–22‐week anomaly scan has the potential to enhance substantially the performance of screening for fetal CoA and subsequently the detection rate of CoA. Future research should clarify how AI technology can be used to aid in the screening and detection of congenital heart anomalies to improve neonatal outcomes. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. Linked article: There is a comment on this article by Drukker. Click here to view the Editorial. [ABSTRACT FROM AUTHOR]

In this work, we present a novel approach for calibrating material model parameters for soft body simulations using real data. We use a fully differentiable pipeline, combining a differentiable soft body simulator and differentiable depth rendering, which permits fast gradient‐based optimizations. Our method requires no data pre‐processing, and minimal experimental set‐up, as we directly minimize the L2‐norm between raw LIDAR scans and rendered simulation states. In essence, we provide the first marker‐free approach for calibrating a soft‐body simulator to match observed real‐world deformations. Our approach is inexpensive as it solely requires a consumer‐level LIDAR sensor compared to acquiring a professional marker‐based motion capture system. We investigate the effects of different material parameterizations and evaluate convergence for parameter optimization in both single and multi‐material scenarios of varying complexity. Finally, we show that our set‐up can be extended to optimize for dynamic behaviour as well. [ABSTRACT FROM AUTHOR]

Probiotics are live microorganisms, which, when administered in adequate amounts, confer a health benefit on the host. Semiactive, non‐replicating bacteria or extracts used in dermocosmetics have interesting properties for skin quality. Vitreoscilla filiformis is cultured by a fermentation process to obtain an extract. It is considered as a probiotic fraction and topical application of this extract has shown activity to strengthen the skin physical barrier function and maintain good homeostasis of skin defenses. Vichy volcanic mineralizing water (VVMW) is a pure, highly mineralized water that has been shown to strengthen the skin against exposome aggressions. This manuscript reviews properties of probiotic fractions used in skin care, especially studies on an extract of V. filiformis grown in a medium containing VVMW (VfeV) and evaluated in combination with VVMW. Skin barrier function: In normal human epidermal keratinocyte cultures, the combination of 10% VVMW and 0.002% VfeV significantly increased transglutaminase, filaggrin, involucrin, claudin‐1, and zonula occludens‐1 in comparison with the controls. Antimicrobial peptide defenses: The combination of 16.7% VVMW and 0.1% VfeV increased the expression of β‐defensin‐4A and S100A7. Skin immune defense functions: In lipopolysaccharide‐stimulated peripheral blood mononuclear cells, the combination of 16.7% VVMW and 0.1% VfeV down‐regulated IL‐8, TNF‐α, IL‐12/IL‐23p40, and increased IL10 and IL‐10/IL‐12 ratio compared to the control. Additionally, the combination of 79% VVMW plus 5% VfeV protected Langerhans cells in skin explants exposed to ultraviolet radiation. In conclusion, the combination of VfeV plus VVMW has properties to strengthen the skin barrier by stimulating skin differentiation and tight junctions, biochemical defenses by stimulating antimicrobial peptides, and cellular immune defenses by increasing the IL‐10/IL‐12 ratio and by protecting Langerhans cells challenged by ultraviolet radiation. [ABSTRACT FROM AUTHOR]

The exposome has an impact on skin from life‐long exposure. Acute short‐term exposure to exposome stressors can also alter skin functions such as skin physical barrier and immune defenses, leading to skin dryness, sensitivity, flares of inflammatory skin conditions, or viral reactivations. Probiotics are defined as live microorganisms, which, when administered in adequate amounts, confer a health benefit on the host. An extract produced by lysing Vitreoscilla filiformis (VfeV) cultured in Vichy volcanic mineralizing water (VVMW) has properties of probiotic fractions. In this review, we present in vivo and ex vivo studies with a dermocosmetic formulation containing 80% VVMW, 5% VfeV, 4% niacinamide (vitamin B3), 0.4% hyaluronic acid, and 0.2% vitamin E (M89PF) to evaluate the clinical efficacy in preventing and repairing stressed skin. Skin barrier benefits of M89PF were shown in studies after the skin was exposed to sudden thermal changes, after skin irritation by tape stripping, and in sleep‐deprived women. M89PF significantly accelerated skin renewal compared to untreated skin. Skin antioxidant defense activity of M89PF was shown after exposure to stress from UVA plus cigarette smoke aggression. Skin microbiome recovery after acute stress from a harsh cleanser was significantly better in M89PF‐treated skin compared to bare skin. Clinical benefits of M89PF on correcting clinical signs of stressed skin were shown in both Caucasian and Asian women exposed to a stressful lifestyle and various external (pollution, tobacco smoking, solar radiation) and internal (poor sleep, stressful work, unbalanced diet, and alcohol consumption) exposome factors. M89PF also showed depigmenting properties on dark spots in Asian women. Further clinical studies are now warranted to evaluate the efficacy of M89PF as adjuvant care to prevent and repair skin barrier disruption and reinforce skin defenses in skin exposed to acute stresses. [ABSTRACT FROM AUTHOR]

Exposome aggressions are known to weaken certain skin functions, such as skin barrier and skin defense functions. Vichy volcanic mineralizing water (VVMW) percolates through volcanic and magmatic rocks in the Auvergne region in France to create a pure, highly mineralized water containing 15 minerals for a total mineral concentration of 5.2 g/L. Here, we provide an overview of the main results of in vitro and ex vivo studies (keratinocyte cultures, 3D reconstructed skin model, skin explants) and clinical studies to evaluate the effect of VVMW on key skin functions to help elucidate how it counteracts exposome aggressions on the skin. Properties to strengthen the skin barrier: VVMW stimulated the synthesis of tight junction proteins and keratinocyte differentiation markers in vitro. In clinical studies, VVMW accelerated cell turnover and improved skin hydration. Properties to strengthen skin antioxidant defense: VVMW stimulated the expression of antioxidant defense markers and had a higher stimulatory effect than a competitor thermal water on the expression of superoxide dismutase, catalase, and glutathione peroxidase in keratinocytes in vitro. In vivo, VVMW restored endogenous catalase activity after exposure to UVA radiation. Anti‐inflammatory action: VVMW reduced substance P‐induced inflammation ex vivo and lactic acid‐induced stinging in vivo. Topical application of VVMW in subjects with sensitive skin showed soothing and decongestant effects by reducing skin dryness and erythema. After sodium lauryl sulfate ‐induced skin barrier disruption, recovery from redness and erythema was faster following application of VVMW compared to a competitor water or untreated skin. These studies illustrate that VVMW has unique properties to repair and regenerate the skin barrier, as well as to strengthen antioxidant and immune defenses, which help protect the skin against exposome aggressions. [ABSTRACT FROM AUTHOR]

Copyright of International Journal of Cosmetic Science is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary: The objective of this study was to document the strongylid infection status of stabled horses residing in an arid environment with limited access to pasture. Faecal parasite examinations were conducted in a private equine practice in Southern California over a period of 7 years, from 2012 to 2018, from a variety of horses in seven different locations; not all horses living at these locations were studied. Results of all faecal examinations were obtained and tabulated, as to both total number of horses examined, as well as individual animals followed with at least four consecutive bi‐annual faecal examinations over a 2‐year period. A total of 851 faecal tests on 79 individual horses were performed during the 7‐year study period, and 78 (9%) were strongyle positive. By the end of the study period, during which horses were monitored and treated according to faecal flotation tests, 97% of 117 faecal flotation tests were negative for strongyle parasites. In conclusion, in a population of 79 adult horses living in dry, arid conditions, with little or no access to pasture, frequent deworming for strongylid parasites would appear to be less necessary than in other environments. Regular faecal monitoring of horses in such conditions is appropriate for determining the necessary level of anthelmintic intervention. [ABSTRACT FROM AUTHOR]

I Dear Editor i , During menopause, oestrogen deprivation occurs after the end of ovulation, reduction of ovarian hormones and increased androgen levels which trigger skin ageing.[1] Skin ageing is associated with an increase in extensibility and a reduction in elasticity. The loss of skin elasticity was significantly reported more often by MPW (70.1%, I P i < 0.001) than by NMPW (31.4%); differences were also significant ( I P i < 0.001) regarding the occurrence of pigmentation spots (57.9% vs. 26.4%), dryness (58.7% vs. 44.1%) and wrinkles (60.8% vs. 30.8%). 2 Brincat M, Kabalan S, Studd JW, Moniz CF, de Trafford J, Montgomery J. A study of the decrease of skin collagen content, skin thickness, and bone mass in the postmenopausal woman. [Extracted from the article]

Purpose: The aim of this study was to develop and gather validity evidence for a standardised test of competence in Focused Assessment with Sonography for Trauma (FAST) and to define the appropriate cut-off point in simulation-based learning of the FAST protocol.Methods: A 20-item simulation-based test for assessing competence in FAST was created. The test was administered to thirteen novices and twelve radiologists experienced in abdominal ultrasound diagnostics. The Contrasting Groups' method was used to establish a credible passing score.Results: The internal consistency was high (Cronbach's α = 0.90) and the test had good discriminatory ability (P < .001). The mean score was 16.9 (95% CI: 15.5-18.3) in the experienced group and 8.0 (95% CI: 5.8-10.2) in the novice group, corresponding to 85% and 40% of the total score, respectively. A pass/fail standard of 14 points was established using the Contrasting Groups' method.Conclusions: The FAST simulation-based test provided valid assessment of competence in FAST. The FAST test could be used to guide training and ensure basic competence of physicians using FAST. [ABSTRACT FROM AUTHOR]

Summary: Background: Primary sclerosing cholangitis is a progressive liver disease with a remarkably variable course. Biomarkers of disease activity or prognostic models predicting outcome at an individual level are currently not established. Aim: To evaluate the prognostic utility of four biomarkers of basement membrane and interstitial extracellular matrix remodeling in patients with primary sclerosing cholangitis. Methods: Serum samples were available from 138 large‐duct primary sclerosing cholangitis patients (of which 102 [74%] with IBD) recruited 2008‐2012 and 52 ulcerative colitis patients (controls). The median follow‐up time was 2.2 (range 0‐4.3) years. Specific biomarkers of type III and V collagen formation (PRO‐C3 and PRO‐C5, respectively) and type III and IV collagen degradation (C3M and C4M, respectively) were assessed. The Enhanced Liver Fibrosis test, including procollagen type III N‐terminal peptide, tissue inhibitor of metalloproteinase‐1 and hyaluronic acid was assessed for comparison. Results: All markers were elevated in primary sclerosing cholangitis compared to ulcerative colitis patients (P < 0.001). PRO‐C3 showed the largest difference between the two groups with a threefold increase in primary sclerosing cholangitis compared to ulcerative colitis patients. Patients with high baseline serum levels of all markers, except C3M, had shorter survival compared to patients with low baseline serum levels (P < 0.001). Combining PRO‐C3 and PRO‐C5 the odds ratio for predicting transplant‐free survival was 47 compared to the Enhanced Liver Fibrosis test's odds ratio of 11. Conclusions: Extracellular matrix remodeling is elevated in primary sclerosing cholangitis patients compared to ulcerative colitis patients. Furthermore, the interstitial matrix marker PRO‐C3 was identified as a potent prognostic marker and an independent predictor of transplant‐free survival in primary sclerosing cholangitis. [ABSTRACT FROM AUTHOR]

Summary: Background: Strongylus vulgaris is re‐emerging in horses kept under surveillance‐based parasite control regimens. Information on nonstrangulating intestinal infarction associated with S. vulgaris is needed to improve recognition of the condition. Objective: To describe the typical clinical presentation, laboratory findings, gross pathology, treatment and outcome of horses with nonstrangulating intestinal infarction. Study design: Retrospective case series. Methods: Nonstrangluating intestinal infarction was diagnosed in 30 horses with a localised intestinal infarction with concurrent signs of S. vulgaris migration and no signs of intestinal strangulation or enterocolitis. Data were obtained from medical records in the period 2008–2016. Long‐term follow‐up information was obtained by telephonic interviews. Levels of S. vulgaris‐specific antibodies were retrospectively assessed. Associations between nonstrangulating intestinal infarction and selected variables were evaluated using Fisher′s exact and Mann–Whitney U tests. Results: The most consistent findings at admission were mild colic of >24 h duration without signs of shock or strangulated intestine, increased peritoneal fluid WBC (>5 × 109/L), increased serum amyloid A (SAA) concentration and a positive S. vulgaris‐specific antibody titre. Medical treatment was attempted in nine horses with none surviving. Exploratory laparotomy was performed in 21 horses. Eleven horses were subjected to euthanasia intraoperatively due to the presumed poor prognosis. Of the nine horses, three (33%) undergoing intestinal resection survived to discharge. The surviving horses were alive and returned to athletic function for at least 2 years following discharge. Main limitations: Only nine of the 30 horses underwent resection of the infarcted intestine, and the prognosis for surgical intervention in nonstrangulating intestinal infarction is, therefore, difficult to estimate. Conclusions: In areas where S. vulgaris is prevalent, nonstrangulating intestinal infarction should be considered as a differential diagnosis in horses presenting with mild colic and peritonitis. Survival of nonstrangulating intestinal infarction is possible in cases where surgical intervention with resection of the infarcted intestine is feasible. The summary is available in Spanish ‐ see Supporting Information. [ABSTRACT FROM AUTHOR]

Identification of fetal kidney anomalies invites questions about underlying causes and recurrence risk in future pregnancies. We therefore investigated the diagnostic yield of next‐generation sequencing in fetuses with bilateral kidney anomalies and the correlation between disrupted genes and fetal phenotypes. Fetuses with bilateral kidney anomalies were screened using an in‐house‐designed kidney‐gene panel. In families where candidate variants were not identified, whole‐exome sequencing was performed. Genes uncovered by this analysis were added to our kidney panel. We identified likely deleterious variants in 11 of 56 (20%) families. The kidney‐gene analysis revealed likely deleterious variants in known kidney developmental genes in 6 fetuses and TMEM67 variants in 2 unrelated fetuses. Kidney histology was similar in the latter 2 fetuses—presenting a distinct prenatal form of nephronophthisis. Exome sequencing identified ROBO1 variants in one family and a GREB1L variant in another family. GREB1L and ROBO1 were added to our kidney‐gene panel and additional variants were identified. Next‐generation sequencing substantially contributes to identifying causes of fetal kidney anomalies. Genetic causes may be supported by histological examination of the kidneys. This is the first time that SLIT‐ROBO signaling is implicated in human bilateral kidney agenesis. [ABSTRACT FROM AUTHOR]

Constitutional mismatch repair deficiency ( CMMRD) is a rare, recessively inherited childhood cancer predisposition syndrome caused by biallelic germline mutations in one of the mismatch repair genes. The CMMRD phenotype overlaps with that of neurofibromatosis type 1 ( NF1), since many patients have multiple café-au-lait macules ( CALM) and other NF1 signs, but no germline NF1 mutations. We report of a case of a healthy 6-year-old girl who fulfilled the diagnostic criteria of NF1 with >6 CALM and freckling. Since molecular genetic testing was unable to confirm the diagnosis of NF1 or Legius syndrome and the patient was a child of consanguineous parents, we suspected CMMRD and found a homozygous PMS2 mutation that impairs MMR function. Current guidelines advise testing for CMMRD only in cancer patients. However, this case illustrates that including CMMRD in the differential diagnosis in suspected sporadic NF1 without causative NF1 or SPRED1 mutations may facilitate identification of CMMRD prior to cancer development. We discuss the advantages and potential risks of this CMMRD testing scenario. [ABSTRACT FROM AUTHOR]

Background: Ultrasound-guided interscalene nerve block with ropivacaine as local anesthetic agent given as boluses or continuous infusion is the preferred pain management after major shoulder surgery. The use of automated intermittent boluses has been shown to be superior to continuous infusion in sciatic and epidural nerve block.Hypothesis: Automated intermittent boluses reduce pain after major shoulder surgery.Methods: Seventy patients aged 18-75 years, scheduled for major shoulder surgery under general anesthesia with interscalene nerve block were included in this randomized controlled trial. Patients were allocated to either automated intermittent boluses with 16 mg ropivacaine every 2 h combined with patient-controlled administration or to a conventional regimen of continuous infusion of 8 mg/h (4 ml/h) of ropivacaine combined with patient controlled administration (2 ml, lockout time 30 min). Pain (Visual Analog Scale, VAS) was assessed every 8 h postoperatively.Results: Fifty-seven patients completed the study, 29 in the continuous infusion group and 28 in the automated intermittent bolus group. Shoulder arthroplasty was performed in 49 (86%) of the cases. There were no significant differences in VAS score from 8 to 48 h post-operatively. No significant difference in opioid usage was observed. The automated intermittent bolus group reported significantly less force on coughing and more hoarseness. A significantly lower volume of ropivacaine was used in the automated intermittent bolus group.Conclusion: Automated intermittent boluses did not reduce pain or rescue opioid consumption compared with continuous infusion of ropivacaine. The automated intermittent bolus group had significantly less force on coughing and more hoarseness. [ABSTRACT FROM AUTHOR]

Background Roux-en-Y gastric bypass is associated with an increased risk of postprandial hyperinsulinaemic hypoglycaemia, but the underlying pathophysiology remains poorly understood. We therefore examined the effect of re-routing of nutrient delivery on gut-islet cell crosstalk in a person with severe postprandial hypoglycaemia after Roux-en-Y gastric bypass. Case report A person with severe postprandial hypoglycaemia, who underwent surgical reversal of Roux-en-Y gastric bypass, was studied before reversal and at 2 weeks and 3 months after reversal surgery using liquid mixed meal tests and hyperinsulinaemic-euglycaemic clamps. The nadir of postprandial plasma glucose rose from 2.8 mmol/l to 4.1 mmol/l at 2 weeks and to 4.4 mmol/l at 3 months after reversal. Concomitant insulin- and glucagon-like peptide-1 secretion (peak concentrations and area under the curve) clearly decreased after reversal, while concentrations of glucose-dependent insulinotropic polypeptide and ghrelin increased. Insulin clearance declined after reversal, whereas clamp-estimated peripheral insulin sensitivity was unchanged. The person remained without symptoms of hypoglycaemia, but had experienced significant weight gain at 15-month follow-up. Discussion Accelerated nutrient absorption may be a driving force behind postprandial hyperinsulinaemic hypoglycaemia after Roux-en-Y gastric bypass. Re-routing of nutrients by reversal of the Roux-en-Y gastric bypass diminished postprandial plasma glucose excursions, alleviated postprandial insulin and glucagon-like peptide-1 hypersecretion and eliminated postprandial hypoglycaemia, which emphasizes the importance of altered gut-islet cell crosstalk for glucose metabolism after Roux-en-Y gastric bypass. [ABSTRACT FROM AUTHOR]

Parasite control in juvenile horses remains a substantial challenge for veterinary practitioners and their clients. This age group is at risk for various types of parasitic disease because their worm burdens tend to be larger and more diverse than in mature horses. This contrast is largely attributable to marked differences in relative levels of acquired immunity. Frequent, perennial anthelmintic treatment is not a sustainable approach for parasite control in this age group, but the simple, surveillance-based parasite control strategies recommended for mature horses are not appropriate for juveniles either. Maneuvering through the early years of a horse's life requires up-to-date knowledge about biology and epidemiology of the parasite species in play as well as local evidence regarding the anthelmintic resistance status of each herd. This article provides an overview of the most important helminth parasites to target in a control programme for juvenile horses, and highlights how the target species change as horses age. Young foals (<2 months) are exposed to Strongyloides westeri and Parascaris spp., whereas the primary target parasite in foals between age 2 months and weaning is Parascaris spp. Beyond weaning, the focus shifts away from ascarids, and the targets instead are strongyles and tapeworms. Gasterophilus spp. and Oxyuris equi are also discussed. [ABSTRACT FROM AUTHOR]

Mortality and morbidity occur commonly following emergency laparotomy, and incur a considerable clinical and financial healthcare burden. Limited data have been published describing the postoperative course and temporal pattern of complications after emergency laparotomy. We undertook a retrospective, observational, multicentre study of complications in 1139 patients after emergency laparotomy. A major complication occurred in 537/1139 (47%) of all patients within 30 days of surgery. Unadjusted 30-day mortality was 20.2% and 1-year mortality was 34%. One hundred and thirty-seven of 230 (60%) deaths occurred between 72 h and 30 days after surgery; all of these patients had complications, indicating that there is a prolonged period with a high frequency of complications and mortality after emergency laparotomy. We conclude that peri-operative, enhanced recovery care bundles for preventing complications should extend their focus on continuous complication detection and rescue beyond the first few postoperative days. [ABSTRACT FROM AUTHOR]

Background While morphological patterns differ, the molecular phenotype of liver fibrosis is considered a stereotypical response to chronic liver injury. However, with different cellular triggers and networks regulating fibrosis, the molecular responses of the injured liver may not be identical. Aim To investigate whether differences in extracellular matrix (ECM) composition of the liver during fibrogenesis in two seemingly similar types of viral hepatitis could be reflected by differences in ECM turnover. Methods Utilising a cross-sectional design, we measured specific ECM protein fragments in plasma from 197 chronic hepatitis B (CHB) patients and 403 chronic hepatitis C (CHC) patients matched for inflammation grade and fibrosis stage. Markers of matrix metalloprotease degraded type I, III, IV and VI collagen (C1M, C3M, C4M, C6M) and type III and IV collagen formation (Pro-C3, P4NP7S). Results P4NP7S, C3M, C4M and C6M were significantly elevated in CHB compared to CHC. In contrast, Pro-C3 was significantly elevated in CHC compared to CHB. Pro-C3, C3M and C4M were increased in parallel with inflammation and fibrosis in both cohorts. C6M and P4NP7S were associated with inflammation and fibrosis only in CHC. Basement membrane collagen fragments P4NP7S and C4M were significantly higher in matched activity and fibrosis cohorts within CHB vs CHC. Conclusion The main parameters to determine extracellular matrix biomarker levels are inflammation, fibrosis, and type of viral insult. Compared to CHC, CHB appears to induce a higher basement membrane turnover. This suggests that there are aetiology-dependent molecular signatures in liver fibrosis that could have pathogenic and diagnostic implications. [ABSTRACT FROM AUTHOR]

Pan-specific prediction of receptor-ligand interaction is conventionally done using machine-learning methods that integrates information about both receptor and ligand primary sequences. To achieve optimal performance using machine learning, dealing with overfitting and data redundancy is critical. Most often so-called ligand clustering methods have been used to deal with these issues in the context of pan-specific receptor-ligand predictions, and the MHC system the approach has proven highly effective for extrapolating information from a limited set of receptors with well characterized binding motifs, to others with no or very limited experimental characterization. The success of this approach has however proven to depend strongly on the similarity of the query molecule to the molecules with characterized specificity using in the machine-learning process. Here, we outline an alternative strategy with the aim of altering this and construct data sets optimal for training of pan-specific receptor-ligand predictions focusing on receptor similarity rather than ligand similarity. We show that this receptor clustering method consistently in benchmarks covering affinity predictions, MHC ligand and MHC epitope identification perform better than the conventional ligand clustering method on the alleles with remote similarity to the training set. [ABSTRACT FROM AUTHOR]

We prove boundedness of pseudodifferential operators on anisotropic mixed-norm Besov and Triebel-Lizorkin spaces. Our proof relies only on general maximal function estimates and provides a new perspective even in the case of spaces without mixed norms. Moreover, we cover the case of Fourier multipliers on the above mentioned spaces. As application we establish boundedness of pseudodifferential operators and Fourier multipliers on anisotropic mixed-norm Sobolev spaces. [ABSTRACT FROM AUTHOR]

Clinical manifestations of acutely stressed skin include dry skin that might accentuate fine lines, oily skin, sensitive skin, pruritus, erythema, pale skin, as well as flares of inflammatory skin conditions such as pigmentation disorders. Vichy volcanic mineralizing water has unique properties to strengthen the skin barrier and skin defenses against exposome aggressions. It is considered as a probiotic fraction because of the way it is produced and its action on the skin after topical application, having shown activity to strengthen the skin physical barrier function and maintain good homeostasis of skin defenses.8 Combining these two ingredients (VVMW and VfeV) may provide synergistic action both on skin barrier and skin immunity. [Extracted from the article]

Equine tapeworm infection has gained increasing attention over the past few decades and a number of research studies have already been published. These focus primarily on the most common of the 3 tapeworm species, Anoplocephala perfoliata, although some new information has also been generated for the other two species, Anoplocephala magna and Anoplocephaloides mamillana. The preponderance of research studies have focused on development and validation of diagnostic techniques for tapeworm detection and the role of these parasites in equine gastrointestinal disease. Several diagnostic techniques have been found useful for diagnosis of A. perfoliata but each has its strengths and weaknesses. Egg counting techniques have been modified to achieve acceptable to good diagnostic performance but the trade-off is often a more time-consuming method. Validation studies indicate that these methods can reliably detect tapeworm burdens above 10 worms. Several enzyme-linked immunosorbent assays (ELISAs) have been developed and made commercially available. These can generate useful information about tapeworm exposure on the herd level but are less reliable for individual diagnosis. Unfortunately, none of the available diagnostic techniques are useful for evaluating anthelmintic treatment efficacy. Coproantigen testing may find use as a future diagnostic modality but further characterisation is required. The large body of scientific evidence supports an association between A. perfoliata infection and certain types of equine colic, although some discrepancy exists between studies. Tapeworm surveillance and control should be considered as part of the overall parasite control strategy. When properly used, the currently available diagnostic tools can guide the veterinarian to make strategic decisions regarding tapeworm control. [ABSTRACT FROM AUTHOR]

An alternative and efficient protocol for the synthesis of methylated pyrrolo-tetrathiafulvalenes have been developed. The key in this new synthetic protocol is 4,6-dimethyl- N-tosyl-(1,3)-dithiolo[4,5- c]pyrrole-2-one, which can be obtained in high yield in a three-step synthetic procedure from 5-dimethyl-3,4-dithiocyanopyrrole. [ABSTRACT FROM AUTHOR]

Reasons for performing study: Parascaris spp. infections can lead to life-threatening small intestinal impactions in foals. Currently available diagnostic techniques cannot estimate the magnitude of an ascarid burden, and hence identify foals potentially at risk of developing impactions. Objectives: To describe and evaluate an ultrasonographic transabdominal scoring technique for monitoring of ascarid burdens in foals and to perform a cost-benefit analysis of the application of this technique. Study design: A transabdominal ultrasonographic technique was validated against ascarid worm counts from 10 foals aged 162–294 days. In a treatment trial, 15 foals were randomly allocated to 3 treatment groups: ivermectin, oxibendazole and no treatment. Blinded ultrasound examinations were performed daily for 5 consecutive days following treatment. Foals were examined ultrasonographically twice by the same investigator, and by different investigators for intra- and interobserver agreement evaluation. Cost-benefit analyses identified threshold values for the probability of ascarid impactions above which the screening method becomes cost-effective. Methods: The ultrasound technique used 3 locations along the ventral midline. An ascarid scoring system was established that assessed the magnitude of ascarid burden ranging from 1–4. The method was validated against worm burdens of 10 worms and above with calculation of diagnostic specificity, sensitivity, and predictive values. Treatment trial data were evaluated statistically using mixed model analysis. Kappa values were generated for intra- and interobserver agreement. Results: Two consecutive examinations were found to detect worm burdens >10 ascarids reliably. Ascarid scores declined in response to both anthelmintic treatments, although differences were not statistically significant. Kappa values indicated fair to moderate intra- and interobserver agreements. The majority of cost-benefit analyses indicated that ultrasound examinations are cost effective when the probability of ascarid impactions is above a range of 0.0001–0.0082 (i.e. 1 in 10,000 to 8 in 1000 foals). Conclusions: The ultrasonographic screening techniques can be a useful tool for monitoring ascarid burdens in foals. [ABSTRACT FROM AUTHOR]

Reasons for performing study: Strongylus vulgaris is a pathogenic helminth parasite infecting horses and was once considered to be the primary cause of colic. Migrating larvae cause ischaemia and infarction of intestinal segments. This knowledge is derived from case reports and experimental inoculations of parasite-naïve foals, and it remains unknown to what extent the parasite is associated with different types of colic. Objectives: To evaluate the role of S. vulgaris as a risk factor for different types of colic in horses. Study design: A retrospective case-control study among horses referred with abdominal pain to the University of Copenhagen Large Animal Teaching Hospital during 2009-2011. Methods: Each colic case was matched with an equid of the same type (pony, Warmblooded or Coldblooded), age, sex and admitted in the same month and year but for problems unrelated to the gastrointestinal tract. Serum samples were analysed for antibodies to migrating S. vulgaris larvae using a recently developed enzyme-linked immunosorbent assay (ELISA). The following 4 case definitions were used: colic sensu lato, i.e. all horses presenting with colic (n = 274), with further subgroups, i.e. undiagnosed colics (n = 48), strangulating obstructions (n = 76) and nonstrangulating infarctions (n = 20). Results: Strongylus vulgaris antibody levels were similar to control values in colics sensu lato and horses with undiagnosed colic. In contrast, nonstrangulating intestinal infarctions were significantly associated with positive S. vulgaris ELISAs (odds ratio 5.33, 95% confidence interval 1.03-27.76, P = 0.05). Also, horses with nonstrangulating infarctions had a significantly higher occurrence of positive ELISAs than horses with strangulating obstructions (odds ratio 3.79, 95% confidence interval 1.34-10.68, P = 0.01) and the colic sensu lato group (odds ratio 3.09, 95% confidence interval 1.20-8.01, P = 0.02). Conclusions: Nonstrangulating intestinal infarction was strongly associated with S. vulgaris-specific antibodies, whereas the more broadly defined colic categories were not associated with positive ELISA results. Thus, the ELISA holds potential to become a helpful adjunct in diagnosis and management of horses with colic. [ABSTRACT FROM AUTHOR]

Parascaris spp. infection is virtually ubiquitous in young foals and worm burdens can achieve high numbers. The most important disease manifestation is impaction of the small intestine, which occurs in a small proportion of infected foals but is associated with a guarded prognosis for survival. Control of Parascaris spp. is complicated by emerging resistance to currently available anthelmintic drug classes. Resistance to macrocyclic lactones has been reported worldwide and a few studies have also documented signs of resistance to pyrantel salts and benzimidazoles. Foals generally develop immunity to Parascaris spp. parasites around age 6 months, but a proportion of weanlings and yearlings can harbour smaller burdens at age 8-10 months. Older horses have occasionally been reported with substantial ascarid burdens as well. Qualitative detection of ascarid eggs has good diagnostic value whereas an actual egg count does not correlate well with the size of the worm burden. A recent investigation documented the applicability of a transabdominal ultrasound technique for semiquantitatively monitoring ascarid burdens in foals. Control of ascarids is complicated by the limited drug classes available for treating this parasite, and by the fact that foals are often concurrently infected with strongyles. In many cases, none of the 3 available anthelmintic classes are simultaneously effective against both parasite groups, so close monitoring is required to select the most appropriate anthelmintic in each case. [ABSTRACT FROM AUTHOR]

Reasons for performing study Traditionally, equine parasite control has relied heavily on frequent routine anthelmintic treatments applied at regular intervals all year round. However, current recommendations aim to employ a more surveillance-based approach and it remains unknown to what extent these recommendations are being implemented on US horse farms. Objectives To describe equine parasite control on Kentucky Thoroughbred farms and evaluate respondents' willingness to pay for various attributes of surveillance-based parasite control strategies. Study design Questionnaire survey performed among the membership of the Kentucky Thoroughbred Farm Managers' Club. Methods The survey collected demographic data and information about current parasite control strategies. Further, respondents were asked to choose between hypothetical parasite control strategies described with a combination of different attributes: costs, time and effort needed, hypothetical disease-risk levels and hypothetical risks of anthelmintic resistance. Data were analysed with multivariable logistic analysis. Results About 26% responded to the survey (n = 112). Most respondents were concerned about anthelmintic resistance and incorporated veterinary advice in defining their deworming programme. However, almost 70% were following a traditional rotational deworming programme with little or no faecal surveillance. Respondents were willing to pay a premium for a product for which there is no known anthelmintic resistance and provided the highest possible decrease in health risks. The number of young horses on the farm, utilisation of veterinarian advice in developing a deworming programme, expressed concern about drug resistance in parasites and having documented drug resistance on the farm all associated significantly with the type of parasite control programme used. Conclusions Traditional approaches for equine parasite control are still widely used in the Kentucky Thoroughbred industry. The data suggest that respondents were only willing to make these changes if they could be given assurance that the surveillance-based approach would prevent anthelmintic resistance and decrease health risks significantly for the horses. [ABSTRACT FROM AUTHOR]

Western flower thrips (WFT), Frankliniella occidentalis ( Pergande) ( Thysanoptera: Thripidae), is a major pest of horticultural crops worldwide. The search for alternative pest management techniques has resulted in increasing interest in the use of kairomones and other behaviour-modifying chemicals to mitigate the impact of this pest. In this study, we determined whether the origin of populations, feeding history, and/or genotype influence the response of WFT to the thrips kairomone lure methyl isonicotinate ( MI) in a Y-tube olfactometer study. Four New Zealand thrips populations were tested: (1) from a commercial glasshouse capsicum crop, (2) from a long-established laboratory colony (>222 generations) kept on chrysanthemums, (3) from a laboratory colony (6-9 generations) kept on French dwarf beans, and (4) thought to be a separate cryptic non-pest species from outdoor yellow tree lupins, Lupinus arboreus Sims ( Fabaceae). In the laboratory tests, significantly more WFT from all four populations chose the MI-laden arm of a Y-tube olfactometer when it contained 1 μl methyl isonicotinate (61.3-73.2%) compared with the blank no-odour arm. No differences in response to MI were found between the two laboratory and the one glasshouse WFT populations. Both laboratory populations and the greenhouse population belonged to the 'glasshouse pest' genotype of WFT. However, the cryptic non-pest WFT genotype responded more strongly to MI than any of the other populations, although the response was only significantly stronger than that of the long-established laboratory population. Significant differences were also found among populations in the average time taken for thrips to make a choice to enter either arm of the Y-tube olfactometer, with the cryptic non-pest lupin genotype taking the shortest time, followed by thrips from the capsicum glasshouse. The results are discussed with respect to the variability in olfactory perception and olfactory behaviour within a species and the relevance to the use of such a kairomone lure in pest management programmes. [ABSTRACT FROM AUTHOR]

Surface-applied agrochemicals have been measured soon after application in drainage water from agricultural fields in various studies. The bypass flow from the soil surface into drains may result from direct macropore connections. In order to identify such macropores, smoke was injected into three 1.15-m deep tile drains in a sandy loam soil using 'smoke oil' and an air blower. Smoke-emitting macropores ( SEM) at the soil surface were characterized as having either strong or weak plumes when compared with reference plumes from 3- and 6-mm wide tubes. A total drain length of 93 m, at three separate sub-drain lines, was investigated after harvest of wheat in autumn 2010 and in spring 2011. Smoke only reached the soil surface layer via earthworm burrows, located in a 1-m wide belt directly above the drain lines. The distributions of SEM across the drain line were similar in autumn and spring. The average number of SEM along the drain lines was 2.3 SEM m−1 drain line. Ponded water in 6-cm wide rings was applied above 52 burrows, including 17 reference burrows that did not emit smoke, and 13 pathways in the soil were examined with dye tracer. Strong SEM marked the entrance of efficient transport pathways conducting surface-applied water and dye tracer into the drain. Water infiltration rates were significantly larger ( P < 0.05) in strong SEM (geometric mean, 195 ml minute−1; n = 19) than in weak SEM (geometric mean, 63 ml minute−1; n = 16) and for the reference burrows (geometric mean, 39 ml minute−1; n = 17). The results suggest that the smoke injection technique is a valuable means of identifying potentially efficient pathways for surface-applied contaminants to enter drains, such pathways being associated primarily with strong SEM. [ABSTRACT FROM AUTHOR]

Frankliniella occidentalis ( Pergande) ( Thysanoptera: Thripidae) (western flower thrips, WFT) is a key pest in a range of crops worldwide. Anthocorid species ( Hemiptera) are important natural enemies of thrips. Several experiments were undertaken to determine whether a thrips lure, methyl isonicotinate ( MI), affected the behaviour of WFT and anthocorids found in outdoor crops. Currently, this volatile compound is used in conjunction with sticky traps for monitoring thrips predominantly in greenhouses in Northern Europe. In the present study, in a nectarine [ Prunus persica ( L.) ( Rosaceae)] orchard and an outdoor capsicum [ Capsicum annuum L. ( Solanaceae)] crop in Spain, blue sticky and white water traps with MI caught significantly more WFT than traps without MI. The volatile compound also significantly increased both blue sticky and white water trap capture of anthocorids - predominantly Orius laevigatus ( Fieber) ( Hemiptera: Anthocoridae) - in the capsicum crop. These results indicate that the behaviour of both WFT and O. laevigatus were altered by the presence of the compound and suggest there is potential to develop novel tools based on MI in conjunction with biological control strategies for thrips management. [ABSTRACT FROM AUTHOR]

Aim To determine whether late gestation under- and overnutrition programme metabolic plasticity in a similar way, and whether metabolic responses to an obesogenic diet in early post-natal life depend on the foetal nutrition history. Methods In a 3 × 2 factorial design, twin-pregnant ewes were for the last 6 weeks of gestation (term = 147 days) assigned to HIGH ( N = 13; 150 and 110% of energy and protein requirements, respectively), NORM ( N = 9; 100% of requirements) or LOW ( N = 14; 50% of requirements) diets. The twin offspring were raised on high-carbohydrate-high-fat ( HCHF; N = 35) or conventional ( CONV; N = 35) diets from 3 days to 6 months of age (around puberty). Then intravenous glucose ( GTT; overnight fasted), insulin ( ITT; fed) and propionate (gluconeogenetic precursor; PTT; both fed and fasted) tolerance tests were conducted to evaluate (hepatic) metabolic plasticity. Results Prenatal malnutrition differentially impacted adaptations of particularly plasma lactate followed by glucose, cholesterol and insulin. This was most clearly expressed during PTT in fasted lambs and much less during ITT and GTT. In fasted lambs, propionate induced more dramatic increases in lactate than glucose, and HIGH lambs became more hyperglycaemic, hyperlactataemic and secreted less insulin compared to the hypercholesterolaemic LOW lambs. Propionate-induced insulin secretion was virtually abolished in fasted HCHF lambs, but upregulated in fasted compared to fed CONV lambs. HCHF lambs had the greatest glucose-induced insulin secretory responses. Conclusion Prenatal malnutrition differentially programmed glucose-lactate metabolic pathways and cholesterol homeostasis. Prenatal overnutrition predisposed for hyperglycaemia and hyperlactataemia, whereas undernutrition predisposed for hypercholesterolaemia upon exposure to an obesogenic diet. Prenatal overnutrition (not undernutrition) interfered with pancreatic insulin secretion by non-glucose-dependent mechanisms. [ABSTRACT FROM AUTHOR]

Oxyuris equi is a well-known equine parasite that has evolved over time from an easily controlled, minor nuisance into an increasingly prevalent pest that may frustrate even the most intensive management efforts. This paper reviews essential features of the biology, epidemiology, pathology, diagnosis and control of Oxyuris infections, and describes the current status of recent biological adaptations. [ABSTRACT FROM AUTHOR]

Aim In the renal collecting ducts, ATP stimulates a Ca2+-activated chloride current. The identity of the channel responsible for the current under physiological conditions is not known and it was hypothesized that TMEM16a is a relevant candidate in the renal collecting duct. Methods The cortical collecting duct cell line M-1 was used as a model of the collecting duct. The ATP induced Ca2+ signalling was imaged in cells loaded with Ca2+-sensitive fluorescent probes using confocal laser-scanning fluorescence microscopy. Chloride current was determined by mounting M-1 cell layers in Ussing chamber. The expression of TMEM16a in human kidney was tested by immunohistochemistry. Results M-1 cells displayed a transient increase in intracellular Ca2+ concentration in response to 100 n m ATP. This response was completely blocked by addition of 100 μ m suramin, indicating that ATP signals through purinergic P2 receptors. Apical addition of 100 n m ATP induced a Cl- current, which was blocked by suramin, DPC and the cysteine-modifying compound MTSET. M-1 cells were found to express TMEM16a at the mRNA and protein level. Functionally, it was found that knock-down of TMEM16a expression in M-1 cells inhibited the ATP induced Cl--current. In human and mouse kidney sections, TMEM16a protein expression was localized to the collecting duct, and TMEM16a was found to be excreted in human urinary exosomes. Conclusion TMEM16a is a Ca2+-activated Cl- channel expressed in the collecting ducts. [ABSTRACT FROM AUTHOR]

Aim Advances in the treatment of rectal cancer have made it possible to perform complex rectal cancer surgery ( COMP- RCS) in patients with primary advanced rectal cancer penetrating beyond the total mesorectal excision planes and in patients with locally recurrent rectal cancer. The aim of this study was to examine health-related quality of life ( HRQoL) before and during the first 2 years after COMP- RCS. Method Between 2001 and 2008, 180 patients were treated with COMP- RCS at Aarhus University Hospital. HRQoL was assessed preoperatively and 3, 6, 12, 18 and 24 months after surgery using three questionnaires. The results were compared with those for patients treated with standard rectal cancer surgery ( STAN- RCS) and with data from the general Danish population ( NORM-data). Results One hundred and twenty-two (68%) patients responded to the questionnaires. Of these 80 (66%) with disease-free survival for 2 years after surgery were included in the main analysis. The lowest level of functioning and the highest degree of symptoms were reported preoperatively. The majority of the HRQo L scales improved or remained stable during the first postoperative year; a decrease was observed for body image only. One year after surgery, HRQoL in patients treated with COMP- RSC was comparable to that for patients treated with STAN- RCS. Lower levels were found for physical and emotional role functioning, compared with NORM-data. Conclusion Patients treated with COMP- RCS experienced improvement in HRQoL in the first year after surgery. One year after surgery, HRQoL was similar to that of patients treated with STAN- RCS. Compared with NORM-data, lower levels were found for physical and emotional role functioning. [ABSTRACT FROM AUTHOR]

ABSTRACT Test control is traditionally performed by a feedback signal from a displacement transducer or force gauge positioned inside the actuator of a test machine. For highly compliant test rigs, this is a problem since the response of the rig influences the results. It is therefore beneficial to control the test based on measurements performed directly on the test specimen. In this paper, fibre Bragg grating (FBG) and Digital Image Correlation (DIC) are used to control a test. The FBG sensors offer the possibility of measuring strains inside the specimen, while the DIC system measures strains and displacement on the surface of the specimen. In this paper, a three-point bending test is used to demonstrate the functionality of a control loop, where the FBG and DIC signals are used as control channels. The FBG strain control was capable of controlling the test within an error tolerance of 20 µm m−1. However, the measurement uncertainty offered by the FBG system allowed a tolerance of 8.3 µm m−1. The DIC displacement control proved capable of controlling the displacement within an accuracy of 0.01 mm. [ABSTRACT FROM AUTHOR]

Background Many patients and healthcare professionals believe that work-related psychosocial stress, such as job strain, can make asthma worse, but this is not corroborated by empirical evidence. We investigated the associations between job strain and the incidence of severe asthma exacerbations in working-age European men and women. Methods We analysed individual-level data, collected between 1985 and 2010, from 102 175 working-age men and women in 11 prospective European studies. Job strain (a combination of high demands and low control at work) was self-reported at baseline. Incident severe asthma exacerbations were ascertained from national hospitalization and death registries. Associations between job strain and asthma exacerbations were modelled using Cox regression and the study-specific findings combined using random-effects meta-analyses. Results During a median follow-up of 10 years, 1 109 individuals experienced a severe asthma exacerbation (430 with asthma as the primary diagnostic code). In the age- and sex-adjusted analyses, job strain was associated with an increased risk of severe asthma exacerbations defined using the primary diagnostic code (hazard ratio, HR: 1.27, 95% confidence interval, CI: 1.00, 1.61). This association attenuated towards the null after adjustment for potential confounders ( HR: 1.22, 95% CI: 0.96, 1.55). No association was observed in the analyses with asthma defined using any diagnostic code ( HR: 1.01, 95% CI: 0.86, 1.19) . Conclusions Our findings suggest that job strain is probably not an important risk factor for severe asthma exacerbations leading to hospitalization or death. [ABSTRACT FROM AUTHOR]

Background New evidence indicates that increased dietary protein ingestion promotes health and recovery from illness, and also maintains functionality in older adults. The present study aimed to investigate whether a novel food service concept with protein-supplementation would increase protein and energy intake in hospitalised patients at nutritional risk. Methods A single-blinded randomised controlled trial was conducted. Eighty-four participants at nutritional risk, recruited from the departments of Oncology, Orthopaedics and Urology, were included. The intervention group ( IG) received the protein-supplemented food service concept. The control group ( CG) received the standard hospital menu. Primary outcome comprised the number of patients achieving ≥75% of energy and protein requirements. Secondary outcomes comprised mean energy and protein intake, body weight, handgrip strength and length of hospital stay. Results In IG, 76% versus 70% CG patients reached ≥75% of their energy requirements ( P = 0.57); 66% IG versus 30% CG patients reached ≥75% of their protein requirements ( P = 0.001). The risk ratio for achieving ≥75% of protein requirements: 2.2 (95% confidence interval = 1.3-3.7); number needed to treat = 3 (95% confidence interval = 2-6). IG had a higher mean intake of energy and protein when adjusted for body weight (CG: 82 kJ kg−1 versus IG: 103 kJ kg−1, P = 0.013; CG: 0.7 g protein kg−1 versus 0.9 g protein kg−1, P = 0.003). Body weight, handgrip strength and length of hospital stay did not differ between groups. Conclusions The novel food service concept had a significant positive impact on overall protein intake and on weight-adjusted energy intake in hospitalised patients at nutritional risk. [ABSTRACT FROM AUTHOR]

ABSTRACT Wind turbine rotor blades are commonly manufactured from composite materials by a moulding process. Typically, the wind turbine blade is produced in two halves, which are eventually adhesively joined along their edges. Investigations of operating wind turbine blades show that debonding of the trailing edge joint is a common failure type, and information on specific reasons is scarce. This paper is concerned with the estimation of the strain energy release rates (SERRs) in trailing edges of wind turbine blades in order to gain insight into the driving failure mechanisms. A method based on the virtual crack closure technique (VCCT) is proposed, which can be used to identify critical areas in the adhesive joint of a trailing edge. The paper gives an overview of methods applicable for fracture cases comprising non-parallel crack faces in the realm of linear fracture mechanics. Furthermore, the VCCT is discussed in detail and validated against numerical analyses in 2D and 3D. Finally, the SERR of a typical blade section subjected to various loading conditions is investigated and assessed in order to identify potential design drivers for trailing edge details. Analysis of the blade section model suggests that mode III action is governing and accordingly that flapwise shear and torsion are the most important load cases.Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Aim Determine the impacts of pre- and early-post-natal nutrition on selected markers of hepatic glucose and fat metabolism. Methods Twin-bearing ewes were fed 100% (NORM) or 50% (LOW) of protein and energy requirements during the last 6-weeks of gestation. Twin-lambs received either a high-carbohydrate high-fat (HCHF) or conventional (CONV) diet from 3 days to 6 months of age (around puberty), whereafter lambs from the four subgroups were slaughtered (16 males/3 females). Remaining lambs (19 females) were fed a moderate diet and slaughtered at 2 years of age (young adults). Results Pre-natal LOW nutrition was associated with increased hepatic triglyceride, ceramide and free fatty acid content in adulthood (not observed in lambs), which was accompanied by up-regulated early-stage insulin signalling as reflected by increased INSRβ and PI3K-p110 protein expression. The HCHF diet increased hepatic triglyceride content in lambs, associated with down-regulated expressions of energy-metabolism-related genes ( GLUT1, PPARα, SREBP1c, PEPCK). These post-natal effects were not observed in adult HCHF sheep, after they had received a moderate (body-fat correcting) diet for 1.5 years. Interestingly, pre-natal LOW nutrition induced permanent alterations in hepatic phospholipids' fatty acid composition. Thus, the amount of linoleic acid (C18 : 2 ∆9,12) was significantly increased and composition of rumen-derived fatty acids were altered, indicating changed composition of rumenal microbiota. Conclusion Hepatic insulin signalling and linoleic and microbial-derived fatty acid content in phospholipids are targets of foetal programming induced by late-gestation undernutrition. Future studies are required to explain their cause-effect associations with increased risks of developing hepatic steatosis and insulin insensitivity in adulthood. [ABSTRACT FROM AUTHOR]

Major histocompatibility complex ( MHC) molecules play a key role in cell-mediated immune responses presenting bounded peptides for recognition by the immune system cells. Several in silico methods have been developed to predict the binding affinity of a given peptide to a specific MHC molecule. One of the current state-of-the-art methods for MHC class I is NetMHCpan, which has a core ingredient for the representation of the MHC class I molecule using a pseudo-sequence representation of the binding cleft amino acid environment. New and large MHC-peptide-binding data sets are constantly being made available, and also new structures of MHC class I molecules with a bound peptide have been published. In order to test if the NetMHCpan method can be improved by integrating this novel information, we created new pseudo-sequence definitions for the MHC-binding cleft environment from sequence and structural analyses of different MHC data sets including human leukocyte antigen ( HLA), non-human primates (chimpanzee, macaque and gorilla) and other animal alleles (cattle, mouse and swine). From these constructs, we showed that by focusing on MHC sequence positions found to be polymorphic across the MHC molecules used to train the method, the NetMHCpan method achieved a significant increase in the predictive performance, in particular, of non-human MHCs. This study hence showed that an improved performance of MHC-binding methods can be achieved not only by the accumulation of more MHC-peptide-binding data but also by a refined definition of the MHC-binding environment including information from non-human species. [ABSTRACT FROM AUTHOR]

Aim Exposure to adverse intra-uterine conditions can predispose for metabolic disorders later in life. By using a sheep model, we studied (i) how programming of glucose-insulin homoeostasis during late gestation is manifested later in life depending on the early post-natal dietary exposure and (ii) whether dietary alteration in obese individuals can prevent adverse outcomes of early life programming. Methods During late gestation, twin-pregnant sheep were fed 100% ( NORM) or 50% ( LOW) of energy and protein requirements. After birth, offspring were exposed to a moderate ( CONV) or high-carbohydrate-high-fat ( HCHF) diet until around puberty. Offspring remaining thereafter (exclusively females) were fed a moderate diet until young adulthood. Results LOW lambs had increased insulin secretory responses during intravenous glucose tolerance tests indicative of reduced insulin sensitivity. HCHF lambs were hypertriglyceridaemic, 75% had mild pancreatic collagen infiltration, and their acute insulin secretory response and insulin clearance during intravenous glucose and insulin tolerance tests, respectively, were reduced. However, NORM- HCHF in contrast to LOW- HCHF lambs had normal glucose tolerance, indicating that later health outcomes are highly influenced by pre-natal nutrition. Dietary alteration normalized glucose-insulin homoeostasis in adult HCHF females, whereas late-gestation undernutrition ( LOW) permanently depressed insulin sensitivity. Conclusion Maintenance of glucose tolerance in sheep exposed to pre-natal undernutrition relied on pancreatic hypersecretion of insulin to compensate for reduced insulin sensitivity. A mismatching high-fat diet in early post-natal life interfered with this pancreatic hypersecretion resulting in reduced glucose tolerance. Early post-natal, but not late pre-natal, impacts on glucose-insulin homoeostasis could be reversed by dietary correction later in life. [ABSTRACT FROM AUTHOR]

Aim To investigate if late gestation under- or overnutrition has similar adverse impacts on visceral adiposity, metabolic and endocrine function in sheep, and if subsequent exposure to a high-fat diet in early post-natal life exaggerates the prenatal programming outcomes later in life. Methods Thirty-six twin-pregnant ewes were fed a NORM (fulfilling 100% of daily requirements for energy and protein), LOW (50% of NORM) or HIGH diet (150% of energy and 110% of protein requirements) during the last 6 weeks of gestation (term = 147 days). Post-natally, the twin lambs were subjected to a high-fat or a moderate diet until 6 months of age (around puberty), where metabolic and endocrine adaptability to fasting was examined, and subgroups of animals were killed. Results Animals exposed to either prenatal under- or overnutrition had reduced subcutaneous fat deposition when fed a high-fat diet, resulting in higher ratios of mesenteric and peri-renal fat relative to subcutaneous fat compared to controls. This was not related to prenatal influences on plasma glucose or insulin. Irrespective of the prenatal diet, high-fat-fed lambs underwent changes resembling the metabolic syndrome with higher plasma glucose, cholesterol, non-esterified fatty acids, triglyceride and lactate combined with abdominal obesity. Peri-renal fat appeared to be a particular target of a high-fat diet post-natally. Conclusion Both prenatal under- and overnutrition predisposed for abdominal adiposity, apparently by reducing the expandability of subcutaneous adipose tissue and induced differential physiological adaptations to fasting. This study does not suggest that exposure to gestational overnutrition will provide a protective effect against development of hyperglycaemia later in life. [ABSTRACT FROM AUTHOR]

Aim According to the World Diabetes Foundation, there is an urgent need to investigate the impact of maternal health and nutrition during pregnancy to understand the background for the accelerating incidence of obesity and type 2 diabetes. In this study, we specifically concentrated on the role of overfeeding during different developmental periods. Methods Sprague- Dawley rats were offered chow or high-fat/high-sucrose diet (chow plus chocolate and soft drink) during gestation and lactation. At birth, offspring were randomly cross-fostered within each dietary group into small and normal litter sizes until weaning, giving four dietary groups. Results At postnatal day 1, offspring from high-fat/high-sucrose-fed dams were heavier and had increased hepatic triglycerides ( TG), hepatic glycogen, blood glucose and plasma insulin compared with offspring from chow-fed dams. Hepatic genes involved in lipid oxidation, VLDL transport and insulin receptor were down-regulated, whereas FGF21 expression was up-regulated. Independent of postnatal litter size, offspring from high-fat/high-sucrose-fed dams aged 21 days had still increased hepatic TG and up-regulated FGF21 expression, while plasma insulin started to decrease. Litter size reduction in offspring from high-fat/high-sucrose-fed dams further increased body weight and adiposity, and up-regulated genes involved in hepatic mitochondrial lipid oxidation and VLDL transport compared with all other groups. Litter size reduction did not have any impact on body weight gain and adiposity in offspring born to chow-fed dams. Conclusion Our results suggest that supplementation of chocolate and soft drink during gestation and lactation contributes to early onset of hepatic steatosis associated with changes in hepatic gene expression and lipid handling. [ABSTRACT FROM AUTHOR]

Background The hepatic venous pressure gradient (HVPG) is an invasive, but important diagnostic and prognostic marker in cirrhosis with portal hypertension (PHT). During cirrhosis, remodelling of fibrotic tissue by matrix metalloproteinases (MMPs) is a permanent process generating small fragments of degraded extracellular matrix (ECM) proteins known as neoepitopes, which are then released into the circulation. Aim To investigate their potential as plasma markers for detection of PHT. Methods Ninety-four patients with alcoholic cirrhosis and 20 liver-healthy controls were included. Clinical and laboratory data of the patients were collected. All patients received HVPG measurement with blood sampling. In these samples, the following degradation or formation markers were measured: C1M (type I-collagen), C3M and PRO-C3 (type III collagen), C4M and P4NP 7S (type IV collagen), C5M (type V collagen), C6M (type VI collagen), BGM (biglycan), ELM (elastin), CRPM (CRP). Results All ECM markers except for CRPM correlated significantly with HVPG. Interestingly, C4M, C5M and ELM levels were significantly higher in patients with HVPG >10 mmHg. Multiple regression analysis identified PRO-C3, C6M and ELM as significant determinants, while the models A and B including PRO-C3, ELM, C6M and model for end-stage liver disease (MELD) provided better description of PHT (r = 0.75, P < 0.0001). The models provided odds ratios of >100 for having clinical significant PHT. Conclusions These novel non-invasive extracellular matrix markers reflect the degree of liver dysfunction. The different degrees of portal hypertension correlated with these circulating neoepitopes. Using a single blood sample, these neoepitopes in combination with MELD detect the level of portal hypertension. [ABSTRACT FROM AUTHOR]

A major challenge in epitope-based vaccine (EV) design stems from the vast genomic variation of pathogens and the diversity of the host cellular immune system. Several computational approaches have been published to assist the selection of potential T cell epitopes for EV design. So far, no thorough comparison between the current methods has been realized. Using human immunodeficiency virus as test case, different EV selection algorithms were evaluated with respect to their ability to select small peptides sets with broad coverage of allelic and pathogenic diversity. The methods were compared in terms of in silico measurements simulating important vaccine properties like the ability of inducing protection against a multivariant pathogen in a population; the predicted immunogenicity; pathogen, allele, and population coverage; as well as the conservation of selected epitopes. Additionally, we evaluate the use of human leukocyte antigen (HLA) supertypes with regards to their applicability for population-spanning vaccine design. The results showed that in terms of induced protection methods that simultaneously aim to optimize pathogen and HLA coverage significantly outperform methods focusing on pathogen coverage alone. Moreover, supertype-based approaches for coverage of HLA diversity were showed to yield only satisfying results in populations in which the supertype representatives are prevalent. [ABSTRACT FROM AUTHOR]

Context In pregnancy, vitamin D insufficiency and deficiency, defined as serum 25-hydroxyvitamin D (25(OH)D) <50 nM, and <25 nM, respectively, may have adverse effects for both mother and child. Prevalence estimates, and identification of subgroups at special risk, may be useful for the planning of preventive strategies. Objective To study the prevalence and risk factors of hypovitaminosis D in early pregnancy. Design and Methods In a cross-sectional study of 1348 women in early pregnancy from the Odense Child Cohort, Denmark, 25(OH)D was determined and correlated to demographic and lifestyle variables (age, nationality, skin tone, parity, prepregnancy body mass index ( BMI), smoking and sun exposure), using multiple linear and logistic regression analyses for all year, or stratified for summer and winter. The risk of vitamin D insufficiency was expressed as odds ratios (OR) with 95% confidence intervals in brackets. Results The prevalence of vitamin D insufficiency and deficiency was estimated to 27·8% and 3·5% respectively. In adjusted analyses, vitamin D insufficiency was directly associated with winter season, OR = 1·89 (1·35-2·63); increasing prepregnancy BMI, OR = 1·06 (1·03-1·10); and smoking, OR = 2·7 (1·34-5·41); but was less frequent in nulliparous, OR = 0·47 (0·33-0·68) and tanned Caucasians, OR = 0·63 (0·41-0·97). Season-specific associations having parental origin from outside Europe in summer, OR = 4·13 (1·41-12·13); in winter smoking, OR = 3·15 (1·19-8·36); and prepregnancy BMI, OR = 1·12 (1·06-1·18). Conclusions Vitamin D insufficiency was widespread in early pregnancy. Associations to smoking, prepregnancy BMI and origin outside Europe varied with season. Multiparity and not being tanned in Caucasians represent new risk factors of vitamin D insufficiency. [ABSTRACT FROM AUTHOR]

Characterization of the peptide-binding specificity of swine leukocyte antigen ( SLA) class I and II molecules is critical to the understanding of adaptive immune responses of swine toward infectious pathogens. Here, we describe the complete binding motif of the SLA-2*0401 molecule based on a positional scanning combinatorial peptide library approach. By combining this binding motif with data achieved by applying the Net MHCpan peptide prediction algorithm to both SLA-1*0401 and SLA-2*0401, we identified high-affinity binding peptides. A total of 727 different 9mer and 726 different 10mer peptides within the structural proteins of foot-and-mouth disease virus ( FMDV), strain A24 were analyzed as candidate T-cell epitopes. Peptides predicted by the NetMHCpan were tested in ELISA for binding to the SLA-1*0401 and SLA-2*0401 major histocompatibility complex class I proteins. Four of the 10 predicted FMDV peptides bound to SLA-2*0401, whereas five of the nine predicted FMDV peptides bound to SLA-1*0401. These methods provide the characterization of T-cell epitopes in response to pathogens in more detail. The development of such approaches to analyze vaccine performance will contribute to a more accelerated improvement of livestock vaccines by virtue of identifying and focusing analysis on bona fide T-cell epitopes. [ABSTRACT FROM AUTHOR]

Background Undernutrition and insufficient energy and protein intake is a common problem in hospitalised patients. The aim of this pilot study was to investigate whether a novel hospital menu would be an effective strategy for increasing nutritional intake in patients at nutritional risk. Methods A historically controlled intervention pilot study was conducted. Forty patients at nutritional risk were offered a novel hospital menu as a supplement to the ordinary hospital menu. The menu consisted of 36 naturally energy-enriched small dishes served on demand 24 h a day. Energy and protein intake were calculated as the mean over a period of 3 days. Results No significant difference in energy and protein intake was observed between the groups; however, a significant ( P = 0.001) time gradient in total energy intake was observed in the intervention group. Moreover, a significant ( P = 0.03) time gradient in energy intake received from the novel menu was observed. The dishes from the novel menu were mainly ordered from 11.00 h to 14.00 h and from 17.00 h to 18.00 h. Conclusions No overall significant differences in energy and protein intake between the groups were found. However, the present pilot study revealed a significant time gradient in total energy intake ( P = 0.001) and in energy intake from the novel menu ( P = 0.03). This indicates the need to include a run-in period when investigating novel hospital menus as a support for patients at nutritional risk. Additionally, food service, available 24 h a day, appears to be unnecessary. [ABSTRACT FROM AUTHOR]